PROJECT SUMMARY/ABSTRACT While the health, social, and economic impacts of opioid addiction on adults and their communities are well known, the impact of maternal opioid use and misuse on the fetus exposed in utero is less well understood. The Outcomes of Babies with Opioid Exposure (OBOE) Study is a longitudinal cohort study to prospectively examine the medical, neuroanatomical, neurodevelopmental, behavioral, and social/family/home outcomes of children who were exposed to opioids in utero as compared with matched controls. The objectives of the OBOE Study are to (1) determine the impact of antenatal opioid exposure on brain structure and connectivity over the first 2 years of life; (2) define medical, developmental, and behavioral outcomes over the first 2 years of life in infants exposed to opioids; and (3) explore whether and how the home environment, maternal mental health, and parenting modify trajectories of brain connectivity and neurodevelopment over the first 2 years of life. We hypothesize that neural connectivity and neuroanatomical volumes are altered by prenatal opioid exposure and that the magnitude of these alterations correlates with developmental and behavioral outcomes. Further, maternal and environmental factors interact with prenatal opioid exposure to influence the trajectories of connectivity, development, and behavior over the first 2 years of life. The OBOE Study Consortium includes four Clinical Sites (Case Western University, Children's Hospital of Pennsylvania, Cincinnati Children's Hospital Medical Center, and the University of Alabama at Birmingham) and an independent Data Coordinating Center (DCC) at RTI International, comprising an Administrative Core and a Research Support Core. The Consortium also includes a neuroimaging core at the Children's National Medical Center, which has an extensive track record of studying brain development in healthy and high-risk fetuses, newborns, and infants using advanced, serial, multimodal MR imaging methods. The DCC and Clinical Sites have a long history of successful collaborations on past and ongoing multisite neonatal follow-up studies, including the NICHD-funded Neonatal Research Network. The proposed study has many innovations including (1) optimizing efficiencies by leveraging ongoing collaborations; (2) integrating both MRI and neurodevelopmental data to obtain a multidimensional evaluation of outcomes; (3) conducting serial MRI assessments to examine trajectories of brain development within the first 2 years of life; (4) using umbilical cord assays to accurately measure amounts of opioid and other substance exposure, which will allow us to examine dose-response effects; and (5) using an innovative tablet application developed by the DCC that will assist with the informed consent process to facilitate participant understanding among this high-risk population.